MicroRNA‑877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion

Abstract

Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.

<p>MiR-1193 Inhibits the Malignancy of Cervical Cancer Cells by Targeting Claudin 7 (CLDN7)</p>

“…[6][7][8] Numerous miRNAs have been identified as oncogenes or tumor suppressors in CC, such as miR-338-3p, 9 miR-211 10 and miR-877. 11 Besides, some miRNAs have been reported to be abnormally expressed and have potential diagnostic or prognostic significance in clinic. 12 Recently, miR-1193, a newly found and poorly studied miRNA, was found to be dysregulated in cutaneous squamous cell carcinoma, T-cell leukemia and breast cancer.…”

Prognostic significance of the expression of metastasis-associated in colon cancer-1 in gynecologic cancers and breast cancer

“…[ 13 – 23 ] Especially, Huang et al study contained 2 independent clinical cohorts. [ 15 ] Nine studies were conducted in China, [ 13 – 16 , 18 – 22 ] 1 study was conducted in Germany [ 17 ] and 1 study was conducted in Bosnia and Herzegovina. [ 19 ] The expression of MACC1 was detected using immunohistonchemistry in 6 studies, [ 13 – 16 , 20 , 22 ] real-time quantitative polymerase chain reaction in 3 studies [ 17 , 18 , 21 ] and other methods in 2 studies.…”

“…[ 15 ] Nine studies were conducted in China, [ 13 – 16 , 18 – 22 ] 1 study was conducted in Germany [ 17 ] and 1 study was conducted in Bosnia and Herzegovina. [ 19 ] The expression of MACC1 was detected using immunohistonchemistry in 6 studies, [ 13 – 16 , 20 , 22 ] real-time quantitative polymerase chain reaction in 3 studies [ 17 , 18 , 21 ] and other methods in 2 studies. [ 23 ] The sample was obtained from tumor tissue in 9 studies [ 13 – 16 , 18 – 22 ] and preoperative serum in 2 studies.…”

“…[ 19 ] The expression of MACC1 was detected using immunohistonchemistry in 6 studies, [ 13 – 16 , 20 , 22 ] real-time quantitative polymerase chain reaction in 3 studies [ 17 , 18 , 21 ] and other methods in 2 studies. [ 23 ] The sample was obtained from tumor tissue in 9 studies [ 13 – 16 , 18 – 22 ] and preoperative serum in 2 studies. [ 17 , 23 ] Four types of cancer were investigated, including ovarian cancer, [ 16 , 17 , 20 , 21 ] breast cancer, [ 15 , 19 , 23 ] cervical cancer [ 14 , 18 , 22 ] and endometrial cancer.…”

Flaming the fight against cancer cells: the role of microRNA-93

“…MiR-205-5p is another oncosuppressor miR involved in inhibition of proliferation of breast cancer cells [49]. It is held that the down-regulation of oncosuppressor miRs occurs during cancer growth and metastasis [50,51].…”